Syringe devices and methods for mixing and administering medication

ABSTRACT

The invention includes a device having a chamber within a syringe. A fluid passageway extends through a syringe piston. A valve is associated with the passageway controlling fluid passage through the piston. The invention includes a piercing structure having a head segment and a body portion, with a channel through the body portion and through at least one surface of the head without passing through the tip. In another aspect the invention encompasses a method of preparing an agent for administration to an individual. A first component is provided within a syringe and a second component is provided within a vial. A closed valve is associated with a fluid passageway between the vial and the syringe barrel through a piston. Valve repositioning allows fluid passage and sliding of the piston joins the first and second components. Repeated sliding of the piston mixes the components to produce the medication agent.

RELATED PATENT DATA

This patent resulted from a divisional application of U.S. patentapplication Ser. No. 11/238,880, which was filed on Sep. 28, 2005 andclaims priority under 35 U.S.C. §119 to U.S. Provisional PatentApplication Ser. No. 60/670,413, which was filed Apr. 11, 2005, and toU.S. Provisional Patent Application Ser. No. 60/618,639, which was filedOct. 13, 2004.

TECHNICAL FIELD

The method pertains to syringe devices, piercing structures, medicationagent preparation systems, mixing and administration systems, methods ofmixing components, and methods of preparing a medication agent foradministration to an individual.

BACKGROUND OF THE INVENTION

Preparation of medicants or medication agents and administration of suchagents to an individual often involves mixing of two or more componentsto form the agent and subsequent delivery of the mixed medicant to theindividual. The mixing of components can typically involve extraction ofone component in fluid form from a vial or other container and transferof such components into a separate container which holds anothercomponent. In particular instances, only a portion of the contents of avial or container is to be utilized for preparing a mixture prior toadministering. Accordingly, the extraction and transfer can involveprecise measuring of one or more components to be mixed.

A variety of problems may occur when utilizing conventional methodologyand devices for mixing and/or administering medicants to an individual.For example, where multiple components are to be mixed, extraction andtransfer of one component and introduction of such component intoanother component can potentially expose one or both of the componentsto a non-sterile or contaminated environment leading to contamination ofthe resulting medicant. Additionally, incomplete extraction or impropermeasurement of one or more components can result in preparation and/oradministration of an improper dosage. In particular instances, once amedicant is mixed the mixture must again be extracted from a vial orcontainer into a syringe prior to administering to an individual. Suchadditional transfer can lead to additional opportunities forcontamination, incomplete extraction of contents and/or inaccuratemeasuring of a component or the resulting medicant. In practice, thereis limited availability of sterile environments for maintainingsterility during transfer and/or mixing of components, or preparationand transfer of medicants. Additional errors can result from use of thewrong diluent to reconstitute the medication. Finally, preparation ofmedicants utilizing multiple components can be tedious and timeconsuming due to factors such as the need to access individuallypackaged items such as separate vials and/or transfer devices, or tomeasure one or more components to be combined to form the medicant.

It would be desirable to develop alternative methodology and systems forpreparation and administration of medicants.

SUMMARY OF THE INVENTION

In one aspect the invention encompasses a syringe device. The deviceincludes a syringe body having a cylindrical housing and a chamberwithin the housing. The device additionally includes a piston having astem, a first end and a second end opposing the first end. The first endis external to the chamber comprised by the syringe body. A fluidpassageway extends through the first end through the stem and throughthe second end of the piston. The syringe device further includes avalve which is associated with the fluid passageway through the pistonsuch that the valve controls selective fluid passage through the piston.A cap can be reversibly attached to the syringe body to provide a fluidseal.

In one aspect the invention encompasses a piercing structure having ahead segment comprising a tip disposed at a first end of the structure.The head has a front surface and an opposing back surface. The piercingstructure additionally includes a body portion comprising a base surfacedisposed at a second end opposing the first end of the structure. Afluid passageway passes through the second end of the structure throughthe body portion and through at least one of the front surface and theback surface of the head without passing through the tip.

In one aspect the invention encompasses a medication agent preparationsystem. The system comprises a syringe having a barrel with an internalchamber, and a piston having a first end, a second end and a fluidpassageway passing longitudinally through the piston. At least a portionof the piston comprising the first end is inserted into the chamber. Apiercing structure having a fluid channel is associated with the secondend of the piston. A vial is disposed proximate and moveable relative tothe tip of the piercing structure. A first component of a medicationagent is disposed within the internal chamber of the syringe barrel andsecond component of the medication agent is disposed within the vial. Avalve is associated with the fluid passageway which passes through thepiston.

In another aspect the invention encompasses a method of preparing amedication agent for administration to an individual. The methodincludes providing a syringe having a syringe barrel and a pistondisposed at an initial position relative to the syringe barrel. A firstcomponent is provided within the syringe barrel and a second componentis provided within a vial. A valve is associated with a fluid passagewaybetween the vial and the syringe barrel with the valve initially beingdisposed in a closed position, blocking fluid passage through thepassageway. The method includes repositioning the valve to allow fluidpassage between the vial and the syringe barrel. After repositioning thevalve, the piston is slid in a first direction to join the firstcomponent with the second component. The first and second components aremixed to produce the medication agent. Mixing can be facilitated byagitating, inverting the device and/or repeated sliding of the piston inopposing directions. The method further includes drawing the medicationagent into the syringe barrel.

In an additional aspect the invention includes a method of preparing acomposition. A packaging material is provided containing a mixing devicein which the mixing device includes a housing having a chamber thereincontaining a first material. The device also includes a piston slideablewithin the chamber with the piston having a length that is greater thanthe length of the chamber. The mixing device further includes acontainer holding a second material. A fluid passageway is disposedlongitudinally through the piston with a valve being associated with thefluid passageway. Without exposing the device to an environment externalto the packaging material the valve is repositioned from a closedposition to an open position. With the valve in the open position thepiston is slid in a first direction from a first position within thechamber to a second position within the chamber. The sliding of thepiston moves one of the first and second components through the piston.The first and second materials are then mixed to form a mixture wherethe mixing comprises sliding the piston in a second direction andsubsequently returning the piston in the first direction. The mixture isthen drawn into the chamber through the piston.

In one aspect the invention encompasses a medicant preparation device.The device includes a syringe barrel which has a first end, a second endand a longitudinal axis therebetween. A piston is insertable with thesyringe barrel through the second end with the piston being slideablewithin the barrel. The device further includes a vial containing amaterial and an adapter component. The adapter component includes a vialhousing portion configured to reversibly receive a vial. The adapteralso has a fitting configured to attach to the syringe at the first end.A first fluid passageway extends through the fitting to a valve, and asecond fluid passageway extends from the valve to the vial housing. Themedicant preparation device additionally includes packaging which isconfigured to allow manipulation of the valve and sliding of the pistonwithout opening of the package.

In a general aspect, the invention includes a device comprising ahousing around a chamber, a piston having a first end, a second end anda fluid passageway between the first and second end with the pistonbeing insertable into the chamber. The device also includes a valveassociated with the fluid passageway such that flow through the fluidpassageway is selectively regulated by the valve.

BRIEF DESCRIPTION OF THE DRAWINGS

Preferred embodiments of the invention are described below withreference to the following accompanying drawings.

FIG. 1 is a side view and partial cross-sectional view of a mixingassembly in accordance with one aspect of the invention.

FIG. 2 is an exploded side view of the assembly shown in FIG. 1.

FIG. 3 is a side view of a portion of a syringe device in accordancewith one aspect of the invention.

FIG. 4 is a side view of a syringe piston in accordance with one aspectof the invention.

FIG. 5 is a perspective view of an exemplary valve according to oneaspect of the invention.

FIG. 6 is a fragmented perspective view of a syringe piston inaccordance with one aspect of the invention.

FIG. 7 is a perspective view of a piercing device in accordance with oneaspect of the invention.

FIG. 8 is a side view of a container which can be utilized in one aspectof the invention.

FIG. 9 is a fragmentary side view and partial cross-sectional view of aportion of a mixing assembly as illustrated in FIG. 1.

FIG. 10 is a fragmentary perspective view of a portion of the mixingassembly illustrated in FIG. 1.

FIG. 11 is an exploded perspective view of a mixing assembly inaccordance with an alternate aspect of the present invention.

FIG. 12 is an exploded perspective view of a mixing assembly inaccordance with another alternate aspect of the invention.

FIG. 13 illustrates an extension housing from a perspective view (PanelA) and an end view (Panel B) in accordance with the aspect shown in FIG.12.

FIG. 14 shows a side view of a mixing device having an integral housingconfiguration in accordance with one aspect of the invention.

FIG. 15A is a side view of an alternate embodiment of a piston inaccordance with one aspect of the invention.

FIG. 15B is an exploded view of the piston structure shown in FIG. 15A.

FIG. 15C is an exploded cross-sectional fragmentary view of the pistonstructure shown in FIG. 15A.

FIG. 15D is a cross-sectional fragmentary sideview of the pistonstructure shown in FIG. 15A.

FIG. 16A is a side view and partial cross-sectional view of a mixingassembly in accordance with an alternative aspect of the invention.

FIG. 16 B is a side and partially cross-sectional view of an adapterportion of the assembly shown in FIG. 16A shown in association with anexemplary vial.

FIG. 17 is a perspective view of an alternate mixing assembly inaccordance with one aspect of the invention.

FIG. 18A is an exploded view of another alternate embodiment of a devicein accordance with the invention.

FIG. 18B is an exploded fragmentary partially cross-sectional view ofthe device shown in FIG. 18A.

FIG. 18C is a fragmentary partially cross-sectional view of the deviceshown in FIG. 18A.

FIG. 19 is a perspective view of a mixing assembly and exemplarypackaging in accordance with one aspect of the invention.

FIG. 20 shows an additional packaging and labeling aspects in accordancewith the invention.

FIG. 21 shows a device and packaging in accordance with an alternateaspect of the invention.

FIG. 22 shows a packaging configuration for a particular aspect of theinvention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

This disclosure of the invention is submitted in furtherance of theconstitutional purposes of the U.S. Patent Laws “to promote the progressof science and useful arts” (Article 1, Section 8).

In general, the invention provides methodology for combining and mixingto produce a mixture and encompasses device configurations to allowcombination and mixing of components. In particular, methodology of theinvention involves combining and mixing components to produce anadministration-ready agent such as a medicant and, in particularaspects, includes administering such agent to an individual.Accordingly, device configurations of the invention allow combination ofseparate components such that the combined and mixed components areadministration-ready. In particular aspects the encompassed devices areadditionally configured for use during administration of theadministration-ready agent. The general concepts and exemplary devicesin accordance with the invention are illustrated in the accompanyingFIGS. 1-22.

Where devices in accordance with the invention are used for preparationof a medicant, the devices are preferably closed-system mixingassemblies. An exemplary mixing assembly 10 in accordance with theinvention is illustrated in FIG. 1. The various components of the mixingassembly 10 are described generally with reference to FIG. 1 and will bedescribed in greater detail with reference to subsequent figures. It isto be understood that the general features described with reference toFIG. 1 are exemplary and the invention encompasses modifications,alternate embodiments and adaptations including but not limited to thosespecifically illustrated in subsequent drawings.

Mixing assembly 10 can comprise a container such as a syringe body (orbarrel) 100 and a piston 200 which has a fluid passageway passingentirely through the length of the piston (discussed further below). Insome instances, a reversibly attached cap (not shown) may be presentproviding a fluid seal at a forward end of the syringe body. A valve 300can be associated with piston 200 and can preferably be configured toallow selective fluid passage through the piston passageway. The mixingassembly can have an extension 600 which can comprise a cylindrical oralternatively shaped housing configured to receive a vial 500 oralternative second container within a chamber or opening within theextension. Assembly 10 can further comprise a puncturing device 400associated with piston 200. Although FIG. 1 and subsequent figuresdepict assemblies as comprising syringes and the description presentsmethodology primarily in terms of preparing a medicant, it is to beunderstood that the invention encompasses alternative container shapesand adaptation of devices for use in mixing of components to formmixtures or agents other than medicants.

As illustrated in FIG. 1, a vial 500 which can be, for example, astandard medicant type vial, can be utilized and extension housing 600can preferably be configured such that vial 500 is slideably insertableinto an internal area of housing 600.

A mixing and administration system comprising mixing assembly 10 asillustrated in FIG. 1 can be described as being a closed-system in thatseparate components of an agent can be combined and mixed withoutexposing the components to an environment external to the mixingassembly. For example, a first component can be provided within vial 500and a second component can be provided within syringe 100. Syringe 100can be capped to retain the second component, with such cap beingreversibly attached to allow removal as appropriate (described below).

As described in greater detail below, the fluid passageway throughpiston 200 preferably extends longitudinally and more preferably alongthe longitudinal axis from a first end of the piston stem through thepiston and out a second end such that fluid communication can beestablished between vial 500 and the chamber of syringe 100.Accordingly, when valve 300 is positioned in an “open configuration”bi-directional fluid flow through the piston passageway is establishedallowing fluid communication between the syringe barrel (preferablycapped) and vial 500.

Referring to FIG. 2, such shows an exploded view of the various generalcomponents of mixing assembly 10. Such view illustrates the generalrelationship of the various components, each of which is describedindependently in subsequent figures. Primarily it is noted withreference to FIG. 2 that piston 200 can comprise an independentlyfabricated seal or stopper portion 208 and that each of valve 300 andpiercing structure 400 can be fabricated independently of the rod orstem portion of the piston. However, it is to be noted that theinvention contemplates alternative aspects where one or more of stopper208, valve 300 and piercing structure 400 are integral with the stemportion of the piston. It is to be additionally noted that extension 600as depicted in FIG. 2 having an open end for receiving vial 500 can befabricated to be independent of piston 200 as illustrated, or can befabricated to be integral with the piston stem portion (not shown).

Referring to FIG. 3, syringe body 100 can comprise a cylindrical housing102 having an interior region or chamber 104 within the housing. Thechamber can be described as having a longitudinal axis extending from afirst end 105 of the syringe body. A second end 106 of the syringe bodyis disposed opposing first end 105. In particular instances, the syringecan comprise a LUER-LOK® (Becton, Dickinson and Company, Corp., FranklinLakes, N.J.) type fitting 108 disposed proximate the second end asillustrated in FIG. 3. Although a Luer-Lok connector is illustrated itis to be understood that the invention contemplates alternativeconnector/fitting configurations. Preferably, connector 108 is able toreceive and preferably reversibly receive a needle, alternative cannula,tubing and/or adaptors which can be utilized, for example, duringadministering of a medicant from within chamber 104 to an individual orin particular instances, for transferring into a distinct container (notshown). In particular applications it can be preferable that syringebody 100 comprise a male Luer-Lok type fitting to allow connection andpreferably reversible connection with a female Luer-Lok fittingcomprised by an administration needle.

Syringe housing 102 can have volume markings such as those illustrated,or can have alternative volume indicators to assist in measuring orverifying volume. Although not specifically illustrated in FIG. 3, a capcan be provided to seal second end 106 (see FIG. 19). The cap canprevent fluid passage from within the syringe barrel during storage,shipping, mixing, etc., and can prevent exposure of medicant componentsto an environment external to the syringe device. The cap can beconfigured to be reversibly attached by Luer-Lok or other fittingmechanism, to allow removal and replacement by an appropriateadministration or transfer attachment.

Syringe body 100 can be a conventional type syringe barrel or can bemanufactured for a particular application in accordance with theinvention. The housing can be fabricated to comprise for example medicalgrade/approved glass or plastic material(s). Exemplary materials whichcan be utilized for syringe housing formation include but are notlimited to polyethylenes, polypropylenes, polycycloolefins, polyvinylchloride (PVC), polyamides (including aliphatic and aromatic variants),polyesters, polycarbonates, copolymer materials including but notlimited to those containing ethylene-diene-propylene monomer (EPDM),polyacrylates, polyurethanes, composites, blends or combinations of suchmaterials, or alternative composite materials.

The volume of the syringe (or alternate container) is not limited to aparticular value and the syringe body can be configured to contain amaximum volume of, for example, from 1 ml to greater than 10 ml.Preferably the syringe volume will be less than or equal to 10 ml. Forpurposes of the present description, the syringe volume refers to thevolume of liquid which the syringe housing is configured to retain andnot the overall volume within internal region 104.

Referring next to FIG. 4, an exemplary piston 200 is illustrated havinga stem portion 201, a first end 204 and a second end 202. The piston canbe described as having a length represented by d₁ extending from firstend 204 to second end 202. The length d₁ is not limited to a particularvalue and can preferably be a value greater than the length thelongitudinal axis of internal syringe chamber 104.

A fluid pathway 206 traverses the length of the piston as illustrated bydashed lines. The diameter of fluid pathway 206 is represented in FIG. 4by “d₂”. In some instances pathway 206 can have a non-uniform diameter,however d₂ as used herein, indicates the minimum diameter of thepassageway. Although d₁ and d₂ are not limited to particular values, itcan be preferable in some instances that the ratio of d₁ to d₂ be atleast about 10:1. Capillary action can be promoted by maximization ofthe aspect ratio of passage length to diameter. Such capillary actioncan assist in creating an airlock within the passage when an associatedvalve is in a closed position, thereby avoiding contact of a liquidcomponent/diluent, with the valve prior to opening of the valve atinitiation of a mixing event (discussed below). However, smaller ratioscan advantageously allow the entirety of the piston stem to bemanufactured as a single piece by, for example, injection moldingtechniques. Accordingly the invention contemplates alternate d₁ to d₂ratios (i.e. less than about 10:1).

As illustrated in FIG. 4, a stopper portion 208 can be provided to bereceived onto second end 202 of piston 201. In contrast withconventional syringe plungers, stopper portion 208 can be configured tohave an opening or channel 210 passing entirely through the stopperallowing fluid passage from within passage 206 through stopper 208.Although a single channel 210 is depicted, the invention contemplatesstopper configurations having a plurality of channels providing fluidpassage through the stopper to/from the passage through the piston stem.As depicted in FIG. 1, piston 200 is configured such that second end 202is receivable within the syringe chamber such that fluid communicationcan be established between the syringe chamber and piston passageway 206through stopper 208 via opening(s) 210 as illustrated in FIG. 4.

Where stopper 208 is formed as an independent structure relative to thepiston stem, the stopper can preferably comprise a relatively softmaterial (with respect to the piston, discussed below). Exemplarymaterials which can be appropriate for fabrication of the stopper basedupon manufacturability, biocompatibility and/or chemical compatibility,and ability to produce a fluid seal include elastomeric materials suchas rubber, butyl, silicones, silanes, polypropylene, polypropylene-EPDM,polyurethanes, and other appropriate plastics, as well as variouscopolymers, blends and combinations thereof.

Referring again to FIG. 4, piston 210 can additionally comprise varioussupporting rings 212, 216 and 217. It is to be understood that suchrings are an optional feature and that stem portion 201 can befabricated to comprise fewer rings than that depicted, to comprise noneof the rings depicted, or to comprise additional rings relative to thosedepicted. The ring structures can additionally be alternately positionedalong the piston stem relative to the positioning shown. In embodimentswherein stopper 208 is an independently formed structure, at least twoof rings 212 are provided for mounting, positioning and retaining thestopper upon the piston. Ring structures 212, 216 and 217 can beadvantageous, for example, for stabilizing and/or maneuvering piston 200and to assist in reducing or avoiding contamination of internal syringebody surfaces during syringe manipulation, especially for embodimentswhere packaging is removed prior to manipulation of the mixing assembly(discussed below).

As additionally illustrated in FIG. 4, piston 200 can comprise anopening 214 extending through piston stem 201. Such opening canpreferably orthogonally intersect fluid passageway 206. Such opening canbe configured to allow insertion of a valve such as the exemplary valvedepicted in FIG. 5. The depicted positioning of opening 214 along thelength of piston stem 201 of FIG. 4 is exemplary. The positioning ofvalve opening 214 is not limited to any particular location and can beanywhere along the length of fluid path 206. It can be preferable insome instances that valve insertion opening 214 be positioned at thehalfway point along distance d₁, or alternately to be more proximate end204 than to end 202. This positioning can advantageously allow ease ofmanipulation of the associated valve.

As depicted in FIG. 1 assembly 10 can be configured such that valve 300is, when disposed in association with opening 214, at least partiallyinsertable within syringe housing 100. However the inventioncontemplates positioning of valve 300 more proximate end 204 than thatdepicted, especially for small volume syringes where a valve such asexemplary valve 300 shown is too large to fit insertably within thesyringe housing. It is to be understood that alternative valve types canbe utilized which can allow insertion or partial insertion of the valveinto the syringe housing even for very small volume syringes.

Exemplary valve 300 is shown in greater detail in FIG. 5. Asillustrated, valve 300 has a body portion 302 and a head portion 304.Head portion 304 can be configured to have extension or protrusion tabs307 and 308. Although FIG. 5 depicts two extension tabs it is to beunderstood that fewer or greater than two extension tabs can beutilized. Extension tabs 307 and 308 can advantageously assist properpositioning and alignment of a fluid passageway 306 which passes throughstem portion 302 of valve 300. The invention additionally contemplatesalternative shapes for head portion 304 relative to the roundconfiguration depicted. For example, the head portion can be arrow-shapeto allow visual and/or tactile indication of valve position. Headportion 304 can also be configured to have alternative or additionalvisual and/or tactile indicators.

Valve body 302 is preferably configured to allow insertion of suchportion into, and in particular instances entirely through, opening 214of piston 200 as illustrated in FIG. 4. Accordingly, and as illustratedin FIG. 5, one or more seal or o-ring 310 can be provided to provide afluid seal within opening 214. Alternatively, a seal can be formed as anintegral part of valve body 302 (not shown). Although opening 214 andthe associated valve 300 are illustrated as being configured such thatthe valve passes entirely through piston stem 201, it is to beunderstood that the invention contemplates alternative configurationswhere opening 214 and an associated valve, span less than an entirety ofthe cross-section of piston stem 201 (not shown). Additionally, althoughFIG. 5 shows a two-way (on/off) stopcock type valve, the inventioncontemplates alternative valve types and appropriate openingconfigurations. For example, rather than the uniform-diametercylindrical valve opening depicted, opening 214 can be configured to beconical, rectangular, or other shape. In such instances, valve body 302can be appropriately shaped to be received within the opening.Alternative valve types such as bi-directional stop valves, slider-typevalves, ball valves, push valves, or gate valves can be utilized and canbe appropriately configured based upon the dimensions of opening 214.

In addition to the single piece piston stem 201 illustrated in FIG. 4the invention contemplates utilization of multipart piston stems.Referring to FIG. 6, an exemplary two part piston stem 201 isillustrated having a first portion 230 and a second portion 232. In theexemplary two-part piston stem illustrated parts 230 and 232 interfaceat the longitudinal position of opening 214 along the piston axis. Parts230 and 232 can be joined by, for example, thermal welding, ultrasonicwelding, radio-frequency welding, adhesive bonding or other appropriatebonding techniques. Alternatively, the two portions can be configured tosnap together or can be secured by various joining structures such pins,clevises, threads or alternative mechanical attachment techniques knownin the art or yet to be developed.

Although the two part piston stem illustrated depicts an interfacebetween the two parts coinciding with the position of valve receivingopening 214 it is to be understood that the positioning of the interfaceis not limited to any particular location and can be, for example,anywhere along the longitudinal length of the piston stem. Appropriatepositioning of the interface and length of the resulting segments can beadapted as appropriate based on ease of manufacture of an appropriatevalve and piston segments. The invention additionally contemplatesmulti-part piston stems having more than two independently manufacturedsegments (not shown).

The piston and the syringe housing portions of the devices of theinvention can typically comprise standard materials utilized forconventional syringe and piston/plunger formation. Typically, thepiston, exclusive of the stopper, will be a relatively hard plastic. Inembodiments where the stopper is integral with the piston, theintegrated piece may be formed of a common plastic material. Exemplaryplastics which can be utilized for piston formation include but are notlimited to polyethylenes, polypropylenes, polycycloolefins, polyvinylchloride (PVC), polyamides (including aliphatic and aromatic variants),polyesters, polycarbonates, polyacrylates, polyurethanes, copolymers,blends, composites, and combinations thereof.

Valve 300 is also not limited to a particular material and canpreferably comprise plastic and/or elastomeric materials. In particularapplications it can be preferable that valve body portion 302 (asillustrated in FIG. 5) comprises an elastomeric material to allow abetter fit and/or seal within the opening 214 of piston stem 201,especially where piston 200 comprises a hard plastic material. Exemplaryelastomeric materials which can be utilized for body portion 302 includebut are not limited to polyurethanes, polypropylene-EPDM, otherpolypropylenes, polysiloxane and/or silicone materials, butyl materials,isoprenes, neoprenes, polyethylenes, and various copolymers, composites,blends or other combinations of such materials. Additional appropriatematerials may include natural rubbers, nitrile rubbers and combinationsthereof. Valve 300, exclusive of o-ring 310, can be constructed as asingle piece and therefore can be formed of a particular material ortype of material. Alternately, head portion 304 can be formedindependently and comprise a material that differs from body portion302. For example, in particular instances head portion 304 can be formedof a hard plastic such as any of those listed above and body portion 302can comprise either a distinct hard plastic material or any of theelastomeric materials listed above.

Referring to FIG. 7, such shows an exemplary piercing structure 400 inaccordance with the invention. Piercing structure 400 can be describedas having a head segment 401 comprising a tip 402 disposed at a firstend. Piercing structure 400 additionally has a stem/body portion 403extending from head portion 401 to a base surface 404 disposed at asecond end of the structure opposing the first end. A channel 406 orother fluid passageway extends through the base surface and preferablythrough an entirety of body portion 403.

The piercing structure 400 shown in 406 illustrates an exemplary shapeand form of head segment 401. As illustrated, head portion 401 can havean external surface comprising a front surface 414 (or upper surface asillustrated) and an opposing back surface 415. In a preferred aspect ofthe invention channel 406 extends less than an entirety of an internallength of head segment 401 such that the channel does not pass throughtip 402. Rather, one or more access holes 408 are provided, for example,through one or both of surfaces 414 and 415. Such configuration wherethe channel does not pass through the tip can advantageously minimize orprevent coring of the septum material or plugging of the channel duringa piercing operation.

Access holes 108 can be disposed orthogonal relative to the longitudinalaxis of channel 406 as depicted in FIG. 7 or can intersect channel 406at an angle of other than 90° (not shown). Additionally, the placementof holes 408 along head segment 401 is not limited to the positionshown. It can be advantageous for holes 408 to be disposed proximate thebody portion of the piercing device to allow such holes to lie justwithin a vial upon piercing. Such can maximize fluid access allowingefficient and complete extraction of vial contents without repositioningof the piercing structure after piercing of a septum or other barriermaterial.

To assist in puncturing and passing of head segment 401 through apunctured material such as, for example, a septum, head portion 401 canbe configured to have one or more edges 410 and 412 be cutting edges,where the term “cutting edge” refers to an edge having a sharpnesssufficient to cut the material being pierced during a piercingoperation. As illustrated in FIG. 7, cutting edges 410 and 412 canpreferably be disposed at the edges of head portion 401 where surfaces414 and 415 meet. Although the figure illustrates two cutting edges itis to be understood that the invention contemplates configurations ofhead portions 401 which have no cutting edges, one cutting edge or morethan two cutting edges. As further illustrated, one or both of surfaces414 and 415 can be beveled. Such surface beveling can additionally aidin passing of head segment 401 through a punctured material.

Body portion 403 of piercing structure 400 can be, for example,cylindrical as illustrated in FIG. 7. Body portion 403 can have auniform circumference throughout its length (not shown) or can havesegments which vary in circumference relative to one another. Forexample, as illustrated in FIG. 7 body portion 403 can have a tubesegment 416 and a base segment 418 where base segment 418 extends frombase surface 404 to tube segment 416. The lengths of segments 418 and416 are not limited to any particular values. Nor is the ratio ofsegment lengths limited to a particular value. Preferably, where baseportion 418 will be seated within another component of a mixing assemblyin accordance with the invention (such as piston 200), the length ofsegment 418 can be such to allow stabilization and/or retention ofpiercing structure 400 in the seated position.

Base portion 418 is preferably of sufficient length and appropriateshape to be securely seated within a seating opening comprised by thepiston (see below). An o-ring or raised portion of base 418 (not shown)can be provided to allow a tight fitting. Accordingly, an appropriateindentation or groove (not shown) can be provided within the seatopening of the piston. In particular instances, a press fit or frictionfit will be utilized for providing sufficient retention of the piercingstructure. Secure joining may optionally be utilized utilizing forexample, an adhesive, welding, or other appropriate joining technique.

With respect to segment 416, such can preferably be of sufficient lengthto pass entirely through a punctured material to allow fluid passageacross the punctured material via access hole 408 and through passageway406. Accordingly, an appropriate length of segment 416 can be determinedby the thickness of a septum or other barrier to be punctured, whilepositioning access hole 408 as near the punctured material as possibleto allow maximum fluid access (discussed above). Further, although thepiercing device is not limited to a particular shape, the “arrowhead”shape configuration depicted in FIG. 7, where head segment 401 has ridgesurfaces 409 which extend laterally outward relative to tube segment416, can assist in stabilizing and retaining the piercing device acrossa septum after puncturing has occurred. Retention of the piercing deviceacross the septum can avoid inadvertent contact of the device by anindividual which could cause injury and/or contamination of themedicant.

Numerous appropriate materials are available for fabrication of piercingdevice 400. Such materials include but are not limited to metals, suchas stainless steel, and various plastics such as polyamides,polyacrylates, polycarbonates, epoxies, polyurethanes, polysulfones,polytherimides, polypropylenes, copolymers, etc., in eitherthermoplastic or thermoset varieties.

In addition to the piercing structure depicted in FIG. 7, and variationsof such configuration, the invention contemplates utilization ofalternate structures to puncture a container barrier. Piston 200 can beadapted accordingly. Alternate structures can include, for example, aneedle or a non-coring piercing structure of alternative shape relativeto the arrowhead design depicted. Such alternative configurations can beespecially useful where multiple vials are to be accessed sequentially(i.e. during preparation of a medicant comprising three or morecomponents).

An exemplary vial 500 which can be utilized as part of a mixing assemblyin accordance with the invention is illustrated in FIG. 8. For purposesof the invention, the term “vial” is not limited to a particularcontainer structure and can be used to refer to various containersincluding containers utilized for parenteral as well as non-parenteralmaterials. Vial 500 can be, for example, a bottle such as illustrated inFIG. 8 having a cap portion 504 and an upper surface 502. Vial 500 canbe a glass bottle or alternatively can be a plastic container or othermaterial utilized conventionally or yet to be developed for retainingand/or accessing a medicant or component thereof.

Referring to FIG. 9, such shows and exemplary engagement configurationof piercing structure 400 and vial 500. In the illustration ofengagement, devise 400 is illustrated as passing through a septum 506within cap portion 504 of vial 500. Accordingly, fluid access isprovided from within vial 500 through access hole 408 into and throughfluid passageway 406.

An exemplary association of puncturing device 400 and a piston 200 inaccordance with the invention is shown in FIG. 10. As illustrated, baseportion 418 (shown in FIG. 9) of the puncturing device is seated withina terminal portion of passageway 206 of piston stem 201. Such terminalportion can preferably be diametrically enlarged relative to otherportions of passageway 206 to allow seating of the piercing structure.FIG. 10 additionally illustrates an exemplary fitting 203 and ridge 205present at the first end 204 of the piston structure. As illustrated,fitting 203 can have an interior area 207 having a base surface 213 withpuncturing device 400 passing through such interior area and basesurface. Although base surface 213 is illustrated as being flat, theinvention contemplates seating configurations where a central portion ofbase surface 213 is raised within area 207 to form a pedestal or boss(not shown), where a central opening within the raised portion is anextension of the fluid passageway through the piston and is configuredfor seating the puncturing device. It can be advantageous to provide araised portion to provide a space between base surface 213 and the topof vial 500. The raised boss configuration can be adjusted to allowproper fitting and/or positioning of a particular vial within thereceiving housing and association with the puncturing device.

Interior area 207 can be of sufficient size to allow a portion of a vialor container, such as cap portion 504 illustrated in FIGS. 8 and 9 to beat least partially insertable within the fitting 203. Additionally,fitting 203 can have an outer diameter of an appropriate size to allowinsertion of fitting 203 within an extension structure (such as thecylindrical housing extension structure shown in FIGS. 1 and 2). Wherefitting 203 is configured for insertion within an extension structure,ridge 205 can preferably be configured to interface with the extensionstructure to allow an appropriate positioning of the extension structurerelative to piston 200 as illustrated in FIG. 1 for example.

Referring again to FIG. 1, a general methodology in accordance with theinvention for the illustrated embodiment can comprise mixing a firstcomponent provided within vial 500 with a second component providedwithin syringe barrel 100. In an initial state prior to the combining ofthe two components, each component is isolated from the other. Piston200 is preferably provided in an initial position relative to thesyringe barrel with valve 300 being initially disposed in an “off”position, blocking fluid passageway through the piston.

In the initial state, syringe 100 is preferably capped or otherwisesealed (not shown) to prohibit passage of material into or out ofsyringe barrel 100 through the second end of the syringe. Piston 200 isinitially disposed in an inserted position through the first end ofsyringe barrel 100 and positioned to allow containment of the secondcomponent within the syringe barrel. Stopper 208 (illustrated in FIG. 2)preferably prohibits passage of the component from within the syringebarrel between the internal surfaces of the housing and the stopper.

While valve 300 is in the off position, vial 500 is positioned bypartial insertion within extension housing 600. It is to be noted thatsuch insertion can, in alternate aspects, be performed by an end user ofthe mixing assembly or can be performed prior to packaging of theassembly (discussed below). Regardless, the vial cap/septum is initiallyprovided to be intact and preferably to be spaced from puncture device400 such that the tip of the puncture device is not in physical contactwith any portion of vial 500 as initially provided.

Once combination and mixing of the separate components is desired, vial500 can be repositioned by, for example, sliding vial 500 farther withinextension 600 to allow device 400 to puncture and be partially insertedthrough the septum or alternate barrier portion of the vial.

Once puncturing has occurred, valve 300 can be rotated or otherwiserepositioned into an open position allowing fluid passage through thepiston. Such repositioning establishes fluid communication between theinterior of vial 500 and the interior of syringe barrel 100 withoutexposing either of the two components to an environment external to themixing assembly. One or both of the first component and second componentcan preferably be in liquid form. Typically, at least the componentwithin the syringe barrel will be in liquid form. Often, the componentwithin vial 500 will be in a dry, powdered or lyophilized form, but mayalternatively be in the form of a liquid, solution, suspension or othermixture.

Where vial 500 contains a non-fluid component, a liquid componentcontained within syringe 100 can be introduced into vial 500 and can becombined with the component within vial 500 by, for example, slidingpiston 200 from an initial position to a second position such thatstopper 208 is repositioned to be nearer the second end of syringe body100. Such sliding motion allows fluid to flow from within the syringechamber through piston 200 and into vial 500 via valve 300. During thepassage the fluid additionally passes through puncturing device 400.

Mixing of the combined components can be performed by, for example, aforward and reverse sliding motion of piston 200 relative to the syringebarrel in a “pumping” type motion. The pumping motion is conducted withthe valve 300 in the open position allowing fluid communication betweenthe syringe barrel and vial 500, typically with the vial being in aninverted position. Alternatively, mixing can be conducted by shaking oragitation of vial 500 and/or the entire mixing assembly, or by acombination of pumping action and shaking, agitating, etc. Once thecomponents have been mixed, the assembly can be prepared for transfer ofthe mixed agent or, where the mixture is an administration-ready agentthe device can be prepared for administrating the agent to anindividual. Alternatively, if additional components are to be combinedwith the mixture, such can be introduced by, for example, flowing intothe syringe via the second end, and mixing as described above.

In order to prepare for transfer and/or administration of the agent, themixture can be drawn into syringe body 100 by, for example, slidingpiston 200 in a rearward motion, typically with the vial in an invertedposition. In other words, piston 200 is partially extracted movingstopper 208 toward the first end of the syringe housing. Upon drawing ofall or an appropriate measured amount of the mixture into the syringebarrel, valve 300 can be rotated or otherwise repositioned into theclosed position blocking fluid passageway from the syringe barrelthrough the piston. The syringe barrel can then be uncapped by, forexample, removal of a cap such as Luer-lok cap fitting. It is to beunderstood that the invention also contemplates performing themixing/preparation of the medicant with a needle fitted to the Luer-lokfitting during the preparation stage. However, the needle is preferablycapped and sealed during such operation or otherwise prevented fromallowing passage or exposure of material from the syringe barrel to anenvironment external to the assembly.

Where a cap is removed in preparation for transfer or administration ofthe agent, an appropriate transfer device such as a needle, cannula,transfer tube and/or other appropriate fitting can be attached to theLuer-lok connection and transfer/administration can occur by slidingforward of the piston within the barrel, thereby expelling the contentsof the barrel through the needle or alternate transfer structure at theLuer-lok end of the syringe. Such transfer is performed with valve 300remaining in the closed position throughout. Alternatively, transfer canbe accomplished by providing assembly 10 into an appropriate syringepump, as will be understood by those skilled in the art.

Referring next to FIG. 11, such shows alternate aspects of the inventionhaving variation relative to the mixing assembly shown in FIGS. 1-10.Components that vary relative to those illustrated in earlier figuresare either given numeric identifiers having a appendant “a” or a uniqueidentifier relative to those used previously. In the embodiment shown inFIG. 11, piston portion 200 a is shown as having lateral rib structures220 a extending lengthwise along stem potion 201 a. Such rib featurescan be similar or identical to those present on conventional syringeplunger devices. The presence of ribs 220 a can provide additionalsupport and thereby strengthen the piston. As illustrated, ringstructures 212 a, 216 a are present at various positions along thelength of the stem portion. It is to be understood that the inventioncontemplates alternate placement and/or alternate numbers of both ringstructures and ribs relative to the exemplary configuration depicted inFIG. 11.

As shown in FIG. 11, one or more of rib structures 220 a can be providedto be gapped in the region of valve receiving opening 214 a. The widthof the gap can be configured to allow sufficient space for insertion ofthe valve and to allow positioning of the head portion of the valvewithin the gap. It is noted that the extension tabs present on the headof the valve can be specifically configured to come into contact with arib upon rotation of the valve head. Such can advantageously allowproper open/closed positioning of the valve and alignment of the fluidpassageway through the valve and piston stem 201 a.

Mixing assembly 10 a as shown in FIG. 11 utilizes an extension portion600 having a groove 602 extending partially along the length of theextension housing. Extension portion 600 can comprise two grooves asillustrated or can comprise fewer or greater number of grooves. Suchgrooves can allow a slight expansion in the interior circumference ofthe extension housing. This feature can allow a tight yet reversible fitto be established between extension housing 600 and vial 500. Forexample, where the internal area 604 of the extension has acircumference which is slightly less than or equal to the maximumcircumference of vial 500, grooves 602 can allow a slight expansion ofthe housing to allow insertion of vial 500. Such configuration canadditionally allow retention of vial 500 within internal region 604until force is applied to extract the vial.

The length of the groove(s) 602 can be configured to allow positioningand stabilization of vial 500 within the housing in a position whichdisposes a septum or cap of vial 500 in a spaced relationship relativeto puncture device 400 (discussed below). The spaced relationship canallow packaging and/or shipping of an assembly as a linearly assembleddevice where the cap of vial 500 remains intact prior to removal of someor all of packaging materials and/or intentional engagement.Accordingly, the length of grooves 602 and the relative length of thegrooves and the overall length of housing 600 can vary with appropriatelengths and length ratios depending upon the relative length andpositioning of device 400 within such housing and the relative size ofvial 500.

An additional alternative aspect of the invention is described withreference to FIGS. 12-13. Referring initially to FIG. 12, such showsvariation of the components of mixing assembly 10 b relative to themixing assemblies described in previous figures. Components that varyrelative to those illustrated in earlier figures are given either anumeric identifier having an appendant “b”, or a unique identifierrelative to those previously used. In the embodiment depicted in FIG.12, piston portion 200 b is shown as having an alternative fitting 203 bconfiguration. Such configuration can allow a portion of extensionhousing 600 b to be received within an internal area of fitting 203 b.As illustrated by the exploded view, puncturing device 400 can be seatedwithin piston 200 b in a manner similar to that described above withrespect to earlier embodiments. Additionally the various rings and finsdepicted in FIG. 12 in association with piston 200 b can be asillustrated or can have any of the alternative configurations describedabove.

Valve 300 b as depicted in FIG. 12 can comprise one or more alignmentmarkers 312 preferably on an upper surface of valve head 304 to allowvisible and/or tactile alignment of the valve upon insertion withinopening 214 b of piston 200 b. Although depicted as molded arrows, it isto be understood that the invention contemplates alternative alignmentmarkers.

The extension 600 b shown in FIG. 12 illustrates aspects of theinvention where the extension housing has a non-uniform outercircumference. As shown, extension housing 600 b can comprise a firstportion 605 b having a smaller circumference than a second portion 606b. Such configuration can allow insertion and seating of portion 605 bwithin the piston fitting configuration 203 b as illustrated.

The features of extension 600 b are described and more fully illustratedwith reference to FIGS. 13A and B. As shown in FIG. 13A, extensionhousing 600 b has an internal area 604 b configured to receive a vialsuch as a standard vial or an alternative container as described above.One or more slots 602 b can extend longitudinally from the receiving endof the extension housing to allow slight expansion of the housing. Insome instances, the receiving/opening end of housing 600 b can have aninternal diameter equal to or slightly smaller than the diameter of avial prior to insertion of the vial. Insertion of the vial can expandthe housing due to the presence of slots 602 b. Such configuration canallow a snug fit and stabilization of the inserted vial. In combinationwith particular packaging aspects (discussed below) slots 602 b canadditionally allow stabilization of vial positioning during storageand/or shipping.

Referring to FIG. 13B, at least a portion of a length of the interiorarea can comprise interior ribs 607 b. Preferably, at least an interiorlength associated with segment 605 b contains ribs 607 b which canassist in positioning and retaining vial 500 (shown in FIG. 12) withinthe extension housing. Such ribs can additionally provide support forthe vial within the housing upon puncturing of a septum or alternativebarrier material.

Although FIG. 13 depicts extension 600 b as having ribs 607 along only aportion of interior sidewalls of opening 604 b, it is to be understoodthat the invention contemplates alternative aspects where ribs areprovided along a portion or an entirety of the interior surface ofsegment 606 b. The interior sidewalls and/or rib portions within housing600 b can be contoured to correspond to an outer shape of vial 500whether the vial is of the conventional shape illustrated or has andalternative vial or container shape.

Although housing configurations having segments of non-equivalentcircumference are illustrated in FIG. 12 as being utilized with a singlepiece piston stem, it is to be understood that the inventioncontemplates utilization of such housing configuration with any of thealternative piston configurations described herein.

In addition to the embodiments described above wherein vial 500 isprovided independently of the piston portion of the assembly theinvention additionally encompasses configurations where a container isintegral with the piston portion as exemplified in FIG. 14. Theexemplary piston 200 c has features having numeric identifiers with anappendant “c” to distinguish from earlier embodiments. It is to benoted, however, that the general concepts and variations of the earlierembodiments can apply equally to the embodiment depicted in FIG. 14. Itis to be additionally noted that in the piston 200 c, stopper portioncan be provided as an independent component or can be an integral partof piston 200 c. Accordingly, stopper 208 c can comprise a material thatdiffers from the piston stem or can be formed of a material identical tothe material utilized for forming piston stem 201 c.

The alternate aspects of the invention depicted in FIG. 14 includevariation of the extension portion to form a container 650 c having abase surface 652 c which opposes first end 204 c of the piston formingan enclosed compartment. Container 650 c can be formed to be integralwith the piston during a common fabrication event (such as molding), orby affixing an independently formed container structure to the fittingportion 203 c of the piston. Alternatively, container portion 650 c canbe reversibly attached to the piston. Attachment (whether permanent orreversible) of an independently formed container to second end 204 c cancomprise insertion of fitting portion 203 c similar to the attachment ofextension portion 600 described above. Joining and affixing of thecontainer portion to the piston can comprise for example a snap-on typejoint or welding.

Alternative integral vial-piston configurations contemplated by theinvention include, for example, providing an opening through the vialportion, for example through base surface 652 c (not shown), which canbe utilized during providing of a medicant component into the vialand/or during drying or lyophilization of the component. Such openingcan be subsequently capped or otherwise sealed.

The material utilized for construction of container 650 c is not limitedto a particular or class of materials. Container 650 c can in particularinstances be formed of a plastic material which can be either a rigidmaterial or a collapsible material.

A component of a medicant or other mixture to be formed can be providedwithin container 650 c and can be isolated from an associated syringebarrel (not shown) by providing a valve into valve receiving opening 214c. An appropriate valve can be, for example, any of the valves describedabove. The component provided in container 650 c can be provided withinthe container prior to attachment of the container or alternatively canbe provided into the integral or attached container via fluid pathway206 through the piston and stopper opening 210 c. The associated valvecan then be closed to prevent the contained component from flowingoutward through the piston.

Where container 650 c is formed independently and is attached to thepiston either reversibly or permanently, an o-ring 230 c can be providedin association with fitting 203 c to provide a fluid seal between thepiston and internal surfaces of container 650 c. Alternatively, otherappropriate sealing techniques can be utilized. It is noted that piston200 c lacks an associated piercing structure. Accordingly, first end 204c of the piston can be modified from earlier discussed configurations tolack accommodation features for the piercing device. Further, theillustrated attachment of container 650 c to piston 200 c is anexemplary configuration and alternative shapes and attachment methodsare contemplated.

Although the integral container/piston structure illustrated is shown tohave rings and ribs 220 c it is to be understood that the ribs and ringsare optional as is the number of such ribs and/or rings, as set forabove with respect to earlier described aspects. Additionally, pistonstem 201 c, which is shown as a single piece, can alternatively comprisemultiple segments as described above (and/or the rotational valve typeconfiguration described below).

Another alternate piston configuration involving a rotational-valve typepiston is exemplified and described with reference to FIGS. 15A-D.Referring initially to FIG. 15A, a piston 200 d is depicted which can beutilized in conjunction with additional mixing assembly componentsdiscussed above. Piston 200 d can comprise a two part piston stem 201 dwhich can optionally include ribs 220 d and/or rings 212 d. Stem 201 dcomprises a first portion 230 d and a second portion 232 d. The lengthsof first segment 230 d and second segment 232 d can be identical or candiffer. The length of each segment and their relative lengths thereofcan be determined by manufacturability and overall length of the piston.Piston 200 d is shown as having an independently formed stopper 208 d.However, it is to be understood that such stopper can be integral withfirst portion 230 d of piston 200 d. An exemplary extension portion 600d is illustrated which can be configured for receiving a vial asdescribed above. As illustrated in FIG. 15, extension portion 600 d canbe integral with second portion 232 d. Such integral piston/extensionconfiguration can be adapted for use with any of the alternative singlepart piston stem aspects described.

Referring next to FIG. 15B, such figure shows an exemplary puncturingdevice 400 d which can be disposed within an internal region ofextension 600 d and which can be positioned to allow communicationbetween an associated vial and fluid pathway 206 d which traverses thelength of piston stem 201 d. First segment 230 d and second segment 232d can be configured to interact to provide valve action. As illustrated,first segment 230 d can comprise a frustoconical protrusion 226 having apair of openings 228 which pass entirely through the frustoconicalprotrusion. Second portion 232 d can be configured to have acorresponding frustoconical interior chamber region 227 configured toreceive protrusion 226. Although a frustoconical shape is illustrated,the invention contemplates protrusion shapes and corresponding receivingchamber shapes other than the exemplary frustoconical shape.

Fluid passageway 206 d is shown as extending partially throughfrustoconical protrusion 226 in a discontinuous manner such that directlongitudinal fluid passage is prevented. Fluid passage 206 d resumes itslongitudinal progress on an opposite side of a solid block of material223. One or more grooves 229 can be disposed within an interior sidewallof second segment 232 d which, when aligned with openings 228 can allowfluid passage from fluid passageway 206 d of first portion 230 d intothe portion of such fluid passageway passing through second portion 232d. Alignment of openings 228 with grooves 229 can be achieved byopposing rotation of portion 230 d relative to portion 232 d. Suchvalve/piston configuration is further described with reference to FIG.15C. As illustrated, protrusion 226 can comprise one or more O-rings 222to allow fluid seal to be formed upon insertion of the protrusion intoreceiving chamber 227.

Referring to second segment 232 d of piston 200 d, a pair of grooves 229is illustrated as being arc shaped grooves formed in the sidewallmaterial of the piston. It is to be understood that alternative shapedgrooves are contemplated and the arc shaped grooves are but oneexemplary configuration. Referring next to FIG. 15D, upon insertion ofthe protrusion into the receiving chamber of second segment 232 d,rotation of part 230 d and 232 d relative to one another can beperformed to align fluid access openings 228 with grooves 229 to allowconnection of passageway 206 via access openings 228 allowing fluidpassageway between segments 230 d and 232 d. Further rotation or reverserotation can be utilized to misalign access openings 228 and groove 229to again close fluid access between the two piston parts.

Although fluid access openings 228 are shown as extending entirelythrough protrusion 226 (see FIG. 15C) it is to be understood that suchopenings can extend less than an entirety of the width of suchprotrusion. Alternatively, access openings 228 can be provided on asingle side of such protrusion. In another alternative, additionalaccess openings can be provided partially or entirely through protrusion226. Similarly, a fewer or greater number than the illustrated twoconnecting grooves can be provided within second segment 232 d.

In addition to the features shown and described above, in particularinstances one or more filters may be utilized for removal ofparticulates prior to administration. Appropriate filter(s) may beincorporated within any of the devices above for example within thefluid passageway through the piston. Additionally or alternatively, oneor more filters may be provided in association with the syringe outlet,either internally or externally to the syringe barrel.

Methodology for mixing components to prepare a mixture utilizing therotational piston type valve configuration illustrated in FIGS. 13A-Dcan be conducted in a manner similar to methodology described withreference to FIG. 1. Using the rotational piston type device, ratherthan rotating or repositioning independent valve component 300illustrated in FIG. 1, first and second segments of the piston would beopposingly rotated to open or close fluid passageway through the pistonat the appropriate stage of the mixing procedure.

Another alternate embodiment of a mixing device in accordance with theinvention is described with reference to FIGS. 16A-B. Referring to FIG.16A, a mixing system 10 e can comprise a syringe 100 and an adapter 700which can be reversibly attachable to the syringe 100 by, for example,providing a female Luer-lok or alternative fitting 708 on a first end ofadapter 700. Syringe 100 can preferably be a conventional syringeutilizing a conventional type piston/plunger 200 e. Adapter 700 can beprovided to have a first fluid passageway 706 (denoted with dashedlines) which passes through female Luer-lok fitting 708 and through asegment of adaptor housing 704 to a valve 800, and a second fluidpassageway segment 707 (denoted with dashed lines) which passes from thevalve 800 to an interior area 703 of a vial housing 702. Althoughdepicted as inline passageways, the invention contemplates passageways706 and 707 being angled or orthogonal relative to one another.

As illustrated in FIG. 16B, internal chamber 703 can be configured toreceive a vial 500 such as, for example, a standard vial. Alternativevials or container types can be utilized as described above. Vialhousing 702 can additionally be configured to contain an associatedpuncture device 400 e which can be similar to or identical to thepuncture devices described above. Insertion of vial 500 into housing 702can be as described above with respect to extension housing 600 withreference to FIGS. 1-10.

Adapter 700 can be formed of any appropriate material and in particularinstances will comprise a plastic material such as any of the plasticmaterials discussed above with respect to syringe housings and pistons.Valve 800 can be any of the valve types discussed above with respect toexemplary valve 300 and can accordingly comprise any of the materialsdescribed with reference to such exemplary valve. Alternatively, adapter700 can be configured to have a rotating type valve system as discussedwith reference to FIGS. 15A-D.

Methodology for mixing independent components to prepare a mixture oradministration-ready agent utilizing the assembly illustrated in FIGS.16A-B can comprise providing a first component in an independent vial500 and providing a second component to be combined and mixed with thefirst component within syringe 100. Syringe 100 and vial 500 are theneach attached to adapter 700. Attachment and puncturing of vial 500 canbe performed as described above with respect to earlier embodimentshaving puncture device 400. The order of attachment of vial 500 andsyringe 100 is not limited to a particular sequence. Preferably, valve800 is in a closed position during attachments of the vial and thesyringe.

Upon assembly, valve 800 can be rotated or otherwise repositioned intoan open position to establish fluid communication between first pathwaysegment 702 and second pathway segment 707 allowing fluid passagethrough the adaptor. Accordingly, fluid communication is establishedbetween vial 500 and syringe 100.

Combining of the first and second components can comprise drawing firstcomponent from vial 500 into the syringe (typically with the vial in aninverted position), or can comprise expelling the second component fromthe syringe into vial 500. Mixture of the components can comprise apumping action as described above with earlier embodiments independentlyor in combination with shaking or otherwise agitating the combinedcomponents. The resulting mixture can be drawn internally within syringehousing 102 e typically while the vial is inverted, and valve 800 can beclosed. Where the mixture is to be subsequently transferred oradministered to an individual, adapter 700 can be removed fromattachment to Luer-lok fitting 108 e and a transfer device such as aneedle, cannula, transfer tube or other transfer structure can beattached to Luer-lok device 108 e. Transfer or administration of themixture can then be achieved by expelling the mixture from the internalchamber within syringe housing 102 e.

An alternative configuration of an adaptor comprised by an assembly isillustrated in FIG. 17. Assembly 10 e′ comprises an alternative adaptorconfiguration 700 e′ relative to that depicted in FIGS. 16A and 16B. Theillustrated adaptor is a “three-way” adaptor having a first segment 710e′ which extends from a three-way valve 800 e′ to a first port 711 e′having a fitting (for example a Luer-lok type fitting) for connectionwith syringe 100 e′. Adaptor 700 e′ additionally includes a secondsegment 712 e′ which extends from the position of valve 800 e′ to asecond port 713 e′. The adaptor additionally has a third segment 714 e′extending from position of valve 800 e′ to a third port 715 e′ which cancomprise a fitting configured for insertion or other association withhousing extension 600 e′ as illustrated. Port 715 e′ can additionally beconfigured to include a piercing structure (not shown) such as thevarious piercing devices described above. Extension portion 600 e′ canhave any of the configurations described above for receiving,stabilizing and/or retaining vial 500 which is shown in a partiallyinserted position within extension 600 e′. Syringe 100 e′ can be astandard conventional syringe with an associated standard type piston200 e′ as illustrated, or can be an alternative syringe configuration,including but not limited to, those described above.

The triple-port adaptor configuration illustrated in FIG. 17 canadvantageously allow introduction and/or removal of material to or fromthe system without dissociation of the syringe and/or vial 500. Forexample, after mixing or preparing a medicant utilizing methodologyanalogous to that described above, the prepared medicant can betransferred or otherwise removed from assembly device 10 e′ through port713 e′. Such transfer or removal can be accomplished by, for example,attaching an appropriate vial, transfer tubing or other transferapparatus to port 713 e′. As illustrated, port 713 e′ has a general typefitting. However, a Luer-lok or other alternative fitting can beutilized as appropriate for attachment to a desired container ortransfer apparatus.

Transfer of material from the assembly via port 713 e′ can be useful forapplications such as IV administration. Alternative administration suchas intramuscular injection, can utilize syringe 100 e′ independentlyafter removal from the assembly. In either instance, piston depressionduring injection can be performed manually or utilizing a syringe pump.

Where a material such as a liquid material for example, is to beintroduced into assembly 10 e′ such introduction can be accomplished bypassage through port 713 e′ and adaptor segment 712 e′. The fluidintroduced can be directed into vial 500 or into syringe 100 e′ asappropriate, by manipulation and positioning of valve 800 e′.Introduction of a fluid into the assembly may be appropriate for examplewhere each of first and second components (within the vial and syringerespectively) is provided in a dry or concentrated form.

The configuration of adaptor 700 e′ illustrated in FIG. 17 can allowlinear alignment of syringe housing 102 e′ and vial 500. It is to beunderstood that the invention additionally contemplates configurationshaving the positions of segments 714 e′ and 712 e′ exchanged such thatvial 500 and syringe body 102 e′ are positioned in an orthogonalarrangement. Further, adaptor 700 e′ can be alternatively configured toprovide segments 710 e′, 712 e′ and 714 e′ at alternative anglesrelative to one another as compared to the orthogonal arrangement shown.Adaptor 700 e′ can optionally have additional segments and ports and cancomprise a higher-order valve relative to the three-way valve depicted.

An additional alternative device configuration in accordance with theinvention is described with reference to FIGS. 18A-18C. Referring toFIG. 18A, assembly 10 f includes a piston 200 f having a rotational typevalve portion disposed at second end 204 f. Valve portion 226 f isfunctionally and structurally analogous to valve portion 226 as shown inFIG. 15B and as described above. However, rather than being disposed ata junction between two portions of a piston stem as illustrated in FIG.15B, valve portion 226 f is disposed at the end of the piston and isinsertable within an opening 557 of a vial cap 550 in accordance withthe invention. Vial cap 550 can be configured for utilization inconjunction with a vial such as the exemplary vial 500 f depicted inFIG. 18A. Vial 500 f can be, for example, a standard medicant vial oralternative container. Vial cap 550 can comprise a base portion 552 anda raised cylindrical or alternatively shaped portion 554 having anopening 557 configured for receiving valve portion 226 f of the pistonstructure.

Upon insertion of valve portion 226 f of the piston into receivingopening 557 of cap 550, the lid/piston combination can function as arotational valve as described above with respect to the rotational valvedepicted in FIG. 15.

Referring next to FIG. 18B, grooves 559 provided within interiorsidewalls of opening 557 can be aligned with fluid passageways 228 f ofvalve portion 226 f. Alignment can provide fluid passageway betweenpassageway 206 f through piston 200 f and a corresponding fluid passage560 which passes from opening 557 through base portion 552 of cap 550,thereby allowing fluid passage between a syringe barrel associated withpiston 200 f and a vial or container associated with cap 552. Fluidalignment and the resulting contiguous passageway is depicted in FIG.18C. Selective fluid communication can be discontinued byopposing-rotation of piston 200 f relative to vial cap 550. In theconfiguration depicted in FIG. 18 A-C, fluid access is provided directlybetween piston 200 f and a vial such that cap 550 can be utilized in anabsence of any piercing structure such as the exemplary piercingstructure described above.

The invention also contemplates utilization of features of the deviceshown in FIG. 18 in combination with one or more features described inalternate embodiments above. In particular applications it can bepreferable to provide multiple fluid barriers between a syringe barreland a vial. Accordingly, the rotational valve configuration depicted inFIG. 18 can be utilized in combination with a second rotational valvesuch as depicted in FIG. 15 or an alternative valve such as describedabove with reference to earlier figures. Such multiple valveconfigurations can advantageously provide an additional safeguardagainst inadvertent contact or mixing of separate components housedwithin a syringe barrel and the medicant vial. Filters, such as thosedescribed above, can additionally be utilized with the device of FIG. 18and variants thereof.

Methodology for utilization of the assembly configuration depicted inFIGS. 18A-C is analogous to the methodology described above (in anabsence of performing steps for piercing a vial cap). Where multiplevalves are provided, fluid communication can be established between thesyringe barrel and the medicant vial by placing each of the valves inthe open position. Mixing can be achieved by, for example, agitationand/or utilization of a piston pumping action. One or both valves can beutilized to discontinue fluid passage, allowing transfer and/oradministration of the prepared medicant.

Although various devices of the invention are described as utilizing asingle vial 500, it is to be understood that the invention encompassesaspects where multiple vials are utilized. In such instances, a firstvial can be removed from the assembly after withdrawing all or a desiredportion of the original vial content, and can be replaced by a secondvial comprising additional or differing material. Accordingly, themixing systems of the invention can be utilized for preparing medicantswhich are made up of three or more components. Mixing of the additionalcomponent can be achieved in a manner analogous to the mixingmethodology discussed above for a corresponding assembly configuration.

Mixing/administration assemblies in accordance with the invention can beshipped as a singular unit including a linear arrangement of the syringedevice and vial. Where an assembly utilizes an independent vial the vialcan be provided in or out of alignment with respect to themixing/administration device. Alternatively, where a vial isindependent, such can be packaged separately from the mixing device.Exemplary packaging in accordance with the invention which can beutilized for a linearly aligned vial and mixing device combination isdescribed with reference to FIGS. 19 and 20.

As illustrated in FIG. 19 a medicant preparation system 20 in accordancewith the invention can comprise a packaging component 900 configured toreceive assembly 10 in linear alignment with a vial 500. Packagingcomponent 900 can be a tray type component as illustrated having amultipart cavity 901, 902, 903. Cavity portion 901 can be configured toapproximate the shape of syringe 100 and associated cap 50. Cavityportion 902 can be shaped to approximate the shape of piston portion200. Cavity portion 903 can be shaped to correspond to the shape of thecombined extension portion (including the fitting to piston 200 in theillustrated embodiment) and an associated vial 500 which can bepartially inserted within housing 600.

In most circumstances it can be preferable that vial 500 be onlypartially inserted with housing 600. In particular instances it can behighly preferred to avoid contact between the piercing structurecomprised by the assembly and the cap or septum comprised by vial 500.Accordingly, a projection 904 can be provided within cavity portion 903which can be insertable within groove 602 of extension housing 600.Projection 904 can be positioned within the groove to stabilize a spacedrelationship between vial 500 and the puncturing device to avoid contactwith the piercing structure prior to removal of the assembly from thepackaging cavity.

Cavity 901, 902, 903 can be configured to be shaped closely to the shapeof the assembly to provide stability to the assembly, preferablystabilizing the position of the piston relative to the syringe barrel.Although the cavities depicted in FIG. 19 mirror the overall shape ofthe assembly, it is to be understood that the cavity can bealternatively shaped for providing position placement and stability.

Packaging component 900 can be formed by, for example, molding.Appropriate materials for packaging component 900 include plasticmaterials, preferably plastics which have suitable strength forproviding positioning and stability of the packaged assembly.

A cover 905 can optionally be provided which can be associated withpackaging component 900. Cover 905 can be provided to cover at least theupper portion/opening of the tray to protect the assembly within thepackaging. In particular instances, cover 900 can be utilized to sealthe packaging and can allow a sterile environment to be created andmaintained within the packaging. The cover can comprise a translucent oropaque material. It can be preferable that at least a portion of thecover be transparent to allow visual inspection of the contents (deviceand/or labels).

As depicted, cover 905 is a sheet of material which may be affixed tocomponent 900. Alternatively, the cover can be a lid type cover whichcan be configured either to fit insertably within the tray opening or tohave at least an upper portion of the tray fit insertably into a lidcavity (not shown).

As illustrated in FIG. 19, one or more labels 910, 912 can be providedin association with assembly 10. A first label 910 can be utilized inassociation with the syringe portion of the device and can provideinformation regarding the contents of the syringe. A second label 912can be provided associated with vial 500 and can be utilized to identifyor provide information regarding the component within the vial. Wherethe medicant is being provided to a particular individual, one or moreof the labels 910 and 912 can contain indicia of the patient. AlthoughFIG. 19 depicts two labels an alternative number of labels can beprovided. The content of the information provided in the label is alsonot limited to any particular content and can provide additionalinformation such as, for example, instructions, warnings, etc.Additionally or alternatively, labeling may be provided in associationwith packaging component 900 and/or 905 (not shown).

The type of label(s) utilized in association with mixing device 10and/or associated via 500 is not limited to a particular label type.Exemplary labels can include bar codes as illustrated. Alternatively oradditionally, one or both of labels 910 and 912 can be a radio frequencyidentification (RFID) label (not shown). Appropriate bar code and/orRFID labeling can be particularly useful for identifying and trackinglots, for record keeping purposes regarding the medicants and/or patientspecific information. Such labeling can provide an additional safetymeasure. For example, in the event of an adverse reaction uponadministering the prepared medicant, information provided on the labelcan be utilized to identify source, lot number, etc., which can in turnbe utilized to track other assembly devices or device componentcontaining material from the identified lot. Such labeling canadditionally be utilized to identify others who may be at risk and/orprovide information regarding the particular reaction, etc.

In the event of adverse reaction or identification of defect, analysisof any material retained within the device after administration can beanalyzed by, for example, analysis techniques including but not limitedto mass spectrometry and/or gas-liquid chromatography. Appropriatereporting to the FDA can then be performed.

Referring to FIG. 20 such shows an additional packaging aspect of theinvention. Assembly device 10 can be provided within a second packagingcomponent 920 which can be a sealed pouch type component as illustrated.Packaging component 920 can preferably provide an enclosed environmentaround device 10 which protects the device and components from exposureto an environment external to packaging component 920. In particularinstances, it can be preferable that the internal environment besterile, especially where medicant components and/or components ofsystem 10 are sterile and are to be maintained in sterile conditionprior to administration.

Packaging component 920 can preferably be translucent and can be formedfrom an appropriate translucent plastic material. The particularmaterial utilized can preferably be selected to provide flexibility toallow manipulation of assembly 10 without opening of packaging component920. In particular, it can be preferable that component 920 be providedto have sufficient internal volume and material flexibility to allow thevial to be manipulated for engagement and puncturing of the cap/septum.Component 920 can preferably also be retained in the sealed conditionwhile manipulating the valve and piston during combining and mixing ofthe medicant components (described above). The ability to prepare themedicant for administration without opening of packaging component 920can minimize or prevent contamination by avoiding exposure to anenvironment external to the packaging component. Upon preparation of anadministration ready medicant, package component 920 can be opened, theprotective cap over the forward end of the syringe can be removed, andtransfer and/or administration can be performed utilizing methodsdescribed above.

Although each can be utilized independently, packaging components 920and 900 depicted in FIGS. 20 and 19 respectively, are configured toallow utilization of both components for a given device. For example, amixing device can be enclosed within packaging component 920 andcomponent 920 and its enclosed device can be inserted into the cavity ofcomponent 900. Accordingly, component 900 can be utilized to providepositioning and stabilization during shipping and storing. The mixingsystem can be removed from packaging component 900 while being retainedwithin component 920. The pouch component 920 can be retained in asealed condition during combination and mixing of the independentcomponents to prepare an administration ready medicant. Where each ofcomponents 920 and 900 are utilized, cover 905 can optionally beprovided.

Although FIGS. 19 and 20 depict a particular mixing systemconfiguration, it is to be understood that similar packaging conceptscan be utilized and adapted for any of the alternative mixing systemsdescribed herein.

Each of FIGS. 19 and 20 depict labels associated only to devicecomponents. Additional labels (not shown) may be associated with thepackaging either by including within the packaging or by affixingexternally to the packaging component(s). The additional labeling canbe, for example, any of the label types discussed above or alternativelabels known to those skilled in the art.

An additional packaging aspect in accordance with the invention isillustrated in FIG. 21. Assembly 10 as illustrated corresponds to theconfiguration illustrated in FIG. 17 and described with referencethereto. Packaging component 920 corresponds to packaging component 920discussed above with reference to FIG. 20. As FIG. 21 illustrates,component 920 can be configured to provide access to assembly 10 by atear strip 921 or alternatively sealed opening. The illustratedpackaging configuration can allow mixing and preparation of a medicantin a sealed environment followed by opening of the package along tearstrip 921. Where appropriate, the prepared medicant can be transferredfrom assembly 10 by, for example, attaching an appropriate transferapparatus to the available port (port 713 as described and illustratedin FIG. 17). Such attachment and transfer can be conducted while all ora portion of assembly 10 remains within the package enclosure.

Where preparation of a medicant involves addition of material intoassembly 10 (described above), such material can be added by, forexample, opening of tear strip 921 and connection of an appropriatetransfer device to the available (non-occupied) port and positioning ofthe valve to allow introduction of the material into the syringe or vialas appropriate. Additional mixing and preparation steps can be performedas described above with or without removal of assembly 10 from packaging920. Transfer or administration of a prepared medicant from the assemblycan comprise placement of the entire assembly into a syringe pump, cancomprise removal of the vial and/or the adaptor from the assembly priorto placement of the syringe into a syringe pump, or can comprise manualmanipulation of the syringe piston.

An alternative tray-type packaging component 900 a is illustrated inFIG. 22. As illustrated, a single cavity 913 can be provided havingraised portions 914, 915, 916 and 917. Raised portions 914-917 can beplatform-type structures having appropriate shape and positioning tostabilize an inserted mixing assembly. Alternative numbers andpositioning of raised portions is contemplated relative to theparticular configuration shown in FIG. 22. Packaging 900 a canadditionally include a raised protrusion (not shown) similar in form andfunction to protrusion 904 depicted in FIG. 19 and described above. Suchprotrusion can be configured to insert into a slot present in theextension housing as described above to retain vial 500 in a non-engagedposition relative to the piercing structure. Although packagingcomponent 900 a is depicted as being configured for the deviceillustrated in FIG. 17, such can be adapted for any of the alternativeembodiments described above. Additionally, packaging component 920 suchas illustrated in FIG. 21 can be utilized simultaneously with component900 a by, for example, providing an assembly within packaging component920 prior to insertion of the assembly into the tray-type component ofthe packaging.

Packaging component 900 a can comprise a lid portion 905 a analogous tothat shown and described with reference to FIG. 19. Appropriate labelingof assembly components (i.e. vial and/or syringe) can be utilizedindependently or in addition to labeling of one or more of the packagingcomponents as described previously.

Where an additional material is to be added into the exemplary assemblydepicted in FIG. 22, lid 905 a, or a portion thereof, can be removedfrom packaging component 900 a followed by opening of a tear strip 921such as that depicted in FIG. 21. An appropriate transfer device can beconnected to the non-occupied port prior to extracting the assembly fromthe package tray. The introduction of material can be achieved bymanipulation of the valve and piston without further removal of theassembly from packaging component 920. Such accessibility to the valveand port can allow introduction of additional materials into theassembly while limiting exposure of the assembly and components thereinto an external environment.

In compliance with the statute, the invention has been described inlanguage more or less specific as to structural and methodical features.It is to be understood, however, that the invention is not limited tothe specific features shown and described, since the means hereindisclosed comprise preferred forms of putting the invention into effect.The invention is, therefore, claimed in any of its forms ormodifications within the proper scope of the appended claimsappropriately interpreted in accordance with the doctrine ofequivalents.

1. A method of preparing a composition, comprising: providing apackaging material containing a mixing device, the mixing devicecomprising: a housing having a chamber therein, the chamber having afirst length and containing a first material; a piston slideable withinthe chamber, the piston having a second length that is greater than thefirst length; a container having a second material therein, thecontainer having a septum; a fluid passageway disposed longitudinallythrough the piston; a piercing structure associated with the piston, thepiercing structure having a base portion, a head portion and a tubeportion extending between the base portion and the head portion; and avalve associated with the piston and orthogonally traversing the fluidpassageway controlling fluid passage through the passageway; withoutexposing the device to an environment external to the packagingmaterial, puncturing the septum of the container with the piercingstructure, the piercing structure being configured such that the tubeportion traverses the septum and the head portion is retained within thecontainer after the puncturing; without exposing the device to anenvironment external to the packaging material, repositioning the valvefrom a closed position to an open position; with the valve in the openposition, sliding the piston in a first direction from a first positionwithin the chamber to a second position within the chamber, the slidingdrawing one of the first and second components through the piston;mixing the first and second materials to form a mixture, the mixingcomprising after sliding the piston in the first direction and with thevalve in the open position, sliding the piston in a second directionopposite the first direction, and subsequently sliding the piston againin the first direction; and drawing the mixture into the chamber throughthe piston.
 2. The method of claim 1 wherein the mixing is performedwithout exposing the mixing device to the external environment.
 3. Themethod of claim 1 wherein the composition is a medication agent andwherein the container is a medical vial.
 4. The method of claim 1wherein the housing is a syringe housing.
 5. The method of claim 1wherein the housing is a syringe housing, wherein the container is amedical vial, and further comprising: after drawing the mixture into thechamber, returning the valve to the closed position; and filtering themixture.